Granule cells are the most numerous neurons in the human brain, making up over half of the total. These small neurons are so densely packed in certain areas that they form distinct structures known as granule cell layers. These layers are not passive collections of cells; they are dynamic processing centers involved in some of the brain’s most important functions.
Where in the Brain is the Granule Cell Layer Found?
The granule cell layer (GCL) is a feature found in several distinct regions of the brain. Its most prominent location is in the cerebellum, the part of the brain at the back of the skull known for its role in coordinating movement and balance. The cerebellar GCL is exceptionally dense, containing more neurons than the rest of the brain combined.
Another location of a granule cell layer is in the hippocampus, a structure deep within the temporal lobe associated with learning and memory. Specifically, the GCL is a component of a hippocampal subregion called the dentate gyrus. Here, the granule cells are involved in forming new memories and distinguishing between similar ones.
A third area where a granule cell layer is present is the olfactory bulb, the brain’s primary center for processing smells. In the olfactory bulb, the GCL helps to refine and modulate sensory information from the nose before it is sent to other parts of the brain for further interpretation.
The Microscopic Structure of the Granule Cell Layer
The granule cell layer’s main component is the granule cell, one of the smallest neurons in the brain, with a cell body of about 5 to 8 micrometers. In the cerebellum, each granule cell extends short dendrites that end in a “dendritic claw” where it receives signals. The axon of a cerebellar granule cell has a T-shape; it rises into the adjacent molecular layer and splits, forming a parallel fiber.
The primary inputs to granule cells in the cerebellum and hippocampus come from nerve fibers called mossy fibers. These fibers originate from other brain regions and carry sensory and motor information. The connections between mossy fibers and granule cell dendrites occur in complex synaptic arrangements known in the cerebellum as cerebellar glomeruli. These are tightly packed zones where a single mossy fiber terminal contacts the dendrites of many granule cells.
Within the granule cell layer, other cell types modulate activity. The Golgi cell, an inhibitory interneuron, receives excitatory signals from granule cells and provides inhibitory feedback to them. This feedback loop helps fine-tune the output of the granule cell layer. The axons of granule cells, the parallel fibers, then project to form thousands of connections with other neurons, like the large Purkinje cells in the cerebellum.
What Does the Granule Cell Layer Do?
In the cerebellum, the GCL’s primary role is in motor control and learning. It processes sensory and motor information that arrives via mossy fibers, helping to coordinate the timing and precision of movements. One theory suggests that the vast number of granule cells allows the cerebellum to perform “pattern separation,” encoding incoming information into a more sparse format. This allows the brain to make fine distinctions between different patterns of neural activity, which is important for refining motor skills.
In the hippocampus, the granule cell layer of the dentate gyrus performs a similar function in the context of memory. It is thought to perform pattern separation for memories, which is the brain’s ability to distinguish between similar experiences. By creating unique neural codes for different memories, the GCL helps prevent them from becoming jumbled. This process is part of forming new episodic memories, and the loss of these neurons has been linked to deficits in spatial memory.
The granule cell layer in the olfactory bulb is dedicated to processing the sense of smell. Here, granule cells receive input from the primary olfactory neurons and regulate the output of the olfactory bulb. This modulation helps in odor discrimination. The inhibitory actions of these granule cells are important in shaping the signals sent to the cerebral cortex for conscious perception of odors.
Development and Adaptability of the Granule Cell Layer
The formation of the granule cell layer begins during embryonic development and, in some brain regions, continues into adulthood. In the cerebellum, granule cells originate from a temporary structure called the external granule layer (EGL). During late embryonic and early postnatal life, progenitor cells in the EGL divide rapidly before differentiating and migrating to form the permanent internal granule cell layer. This proliferation of granule cells is a driver behind the physical enlargement and folding of the cerebellum.
A feature of the granule cell layers in the hippocampus and olfactory bulb is their capacity for adult neurogenesis—the generation of new neurons throughout life. In the hippocampus, new granule cells are born from stem cells in the subgranular zone. These newborn neurons then migrate into the layer, extend axons and dendrites, and gradually integrate into the existing neural circuitry.
The integration of new granule cells allows the hippocampal and olfactory circuits to be continually updated in response to new experiences, providing a form of adaptability, or plasticity. The connections, or synapses, throughout the GCL are also highly plastic, meaning their strength can be modified by neural activity. This synaptic plasticity is a mechanism for learning and memory, allowing circuits to store information.